If the brain operates like a superhighway, Alzheimer’s disease aims to tangle it with inefficient routes and traffic jams, ultimately creating a shutdown.
Researchers are still uncovering how this happens.
Buildup of plaque and tangles
It’s thought that two proteins play a critical role in the development of Alzheimer’s disease – the buildup of amyloid-β into structures called plaques and tau into structures known as neurofibrillary tangles.
For years, the focus of many Alzheimer’s researchers like David Holtzman, M.D., professor and chairman, Department of Neurology, Washington University, St. Louis, Missouri, was into the role of amyloid-β. In healthy brains, amyloid-β is produced and cleared out of the brain on a regular basis, which prevents its accumulation. Researchers focused on the abnormal buildup of amyloid-β in Alzheimer’s disease.
“While it turns out the buildup of amyloid-β does appear to be critical in instigating Alzheimer’s disease, more and more evidence suggests that amyloid-β buildup itself is not directly causing the symptoms and signs of the disease or causing the loss of nerve cells and their connections,” Holtzman says. “Instead, evidence now exists to suggest that tau accumulation is directly leading to many of the symptoms and signs of Alzheimer’s disease and the degeneration of the brain.”
Given this new understanding of the critical role of tau in brain dysfunction, researchers, including Holtzman, have focused on not only whether tau contributes to causing Alzheimer’s disease, but also whether it may be a potential target for treating it.
Tau is a normal protein that lives in the brain and, like the ties on railroad tracks, one of its purposes is to help nerve cells transport the materials they need to function. In Alzheimer’s, tau is thought to fall off the railroad tracks – and form neurofibrillary tangles.
“What happens in Alzheimer’s is that this floppy linear protein, tau, that normally organizes into a highly efficient cable starts to misfold on itself, piles up and destroys neurons, spreading from region to region until many parts of the cortex of the brain are invaded,” says Joel Braunstein, M.D., MBA, president, co-founder and CEO of C2N Diagnostics.
The abnormal accumulation of amyloid-β, but even more importantly tau, are thought to somehow play a critical role in disrupting communication among nerve cells and disturbing processes that cells need to survive.
“Tau starts building up in regions of the brain associated with memory and spatial navigation. Once those areas are affected, the first clinical symptoms of the disease, forgetfulness and often disorientation, begin to show,” says Jim Summers, Ph.D., vice president of neuroscience discovery at AbbVie.
Now researchers are beginning to understand the connection of amyloid-β and tau to Alzheimer’s. “The research community is focused on uncovering how tau misfolds, spreads and forms tangles and its relationship to amyloid-β. Unraveling these mechanisms is pointing us to new approaches to treat the disease,” Summers says.